Limited wedge resection for T1 colon cancer (LIMERIC-II trial) - rationale and study protocol of a prospective multicenter clinical trial.

BACKGROUND: The sole presence of deep submucosal invasion is shown to be associated with a limited risk of lymph node metastasis. This justifies a local excision of suspected deep submucosal invasive colon carcinomas (T1 CCs) as a first step treatment strategy. Recently Colonoscopy-Assisted Laparoscopic Wedge Resection (CAL-WR) has been shown to be able to resect pT1 CRCs with a high R0 resection rate, but the long term outcomes are lacking. The aim of this study is to evaluate the safety, effectiveness and long-term oncological outcomes of CAL-WR as primary treatment for patients with suspected superficial and also deeply-invasive T1 CCs. METHODS: In this prospective multicenter clinical trial, patients with a macroscopic and/or histologically suspected T1 CCs will receive CAL-WR as primary treatment in order to prevent unnecessary major surgery for low-risk T1 CCs. To make a CAL-WR technically feasible, the tumor may not include > 50% of the circumference and has to be localized at least 25 cm proximal from the anus. Also, there should be sufficient distance to the ileocecal valve to place a linear stapler. Before inclusion, all eligible patients will be assessed by an expert panel to confirm suspicion of T1 CC, estimate invasion depth and subsequent advise which local resection techniques are possible for removal of the lesion. The primary outcome of this study is the proportion of patients with pT1 CC that is curatively treated with CAL-WR only and in whom thus organ-preservation could be achieved. Secondary outcomes are 1) CAL-WR's technical success and R0 resection rate for T1 CC, 2) procedure-related morbidity and mortality, 3) 5-year overall and disease free survival, 4) 3-year metastasis free survival, 5) procedure-related costs and 6) impact on quality of life. A sample size of 143 patients was calculated. DISCUSSION: CAL-WR is a full-thickness local resection technique that could also be effective in removing pT1 colon cancer. With the lack of current endoscopic local resection techniques for > 15 mm pT1 CCs with deep submucosal invasion, CAL-WR could fill the gap between endoscopy and major oncologic surgery. The present study is the first to provide insight in the long-term oncological outcomes of CAL-WR. TRIAL REGISTRATION: CCMO register (ToetsingOnline), NL81497.075.22, protocol version 2.3 (October 2022).

Long-term Outcome of Radical Excision Versus Phenolization of the Sinus Tract in Primary Sacrococcygeal Pilonidal Sinus Disease: A Randomized Controlled Trial.

BACKGROUND: Phenolization of pilonidal sinus disease has been shown to have advantages over radical excision with regard to short-term outcome; however, long-term outcomes are essentially lacking. OBJECTIVE: The aim of this randomized controlled trial was to compare the long-term outcome of pit excision and phenolization of the sinus tracts vs radical excision with primary wound closure in pilonidal sinus disease. DESIGN: Single-center, randomized controlled trial. SETTINGS: A primary teaching hospital in the Netherlands. PATIENTS: The study population included patients with primary pilonidal sinus disease presented between 2013 and 2017. INTERVENTIONS: Patients were randomly assigned to either pit excision with phenolization of the sinus tract(s) or excision with primary off-midline wound closure. MAIN OUTCOME MEASURES: The main outcomes included recurrence, quality of life (Short-Form 36), and patient's satisfaction. RESULTS: A total of 100 patients were randomized. Seventy-four patients (77.1%) were available for long-term follow-up. The mean (±SD) time to follow-up was 48.4 (±12.8) months for the phenolization group and 47.8 (±13.5) months for the excision group. No significant difference was found between both groups regarding quality of life. Two patients in the phenolization group (5.6%) and 1 in the excision group (2.6%) developed a recurrence ( p = 0.604). The impact of the whole treatment was significantly less after phenolization ( p = 0.010). LIMITATIONS: The response rate was almost 80% in this young patient population, patients and assessors were not blinded for the type of surgery, and the results are only applicable to primary pilonidal sinus disease. CONCLUSIONS: Because of the previously shown favorable short-term results and the currently reported comparable long-term recurrence rate and quality of life between phenolization and excision, phenolization should be considered the primary treatment option in patients with pilonidal sinus disease. See Video Abstract at http://links.lww.com/DCR/C27 . DUTCH TRIAL REGISTER ID: NTR4043. RESULTADO A LARGO PLAZO DE LA ESCISIN RADICAL FRENTE AL TRATAMIENTO CON FENOL DEL TRACTO SINUSAL EN LA ENFERMEDAD DEL SENO PILONIDAL SACRO COCCGEO PRIMARIO UN ENSAYO ALEATORIO CONTROLADO: ANTECEDENTES:El tratamiento con fenol de la enfermedad del seno pilonidal ha demostrado tener ventajas sobre la escisión radical con respecto al resultado a corto plazo; sin embargo, los resultados a largo plazo aún se encuentran escasos.OBJETIVO:El objetivo de este ensayo aleatorio controlado fue comparar el resultado a largo plazo de la escisión de la fosa del quiste y el tratamiento con fenol de los trayectos sinusales frente a la escisión radical con cierre primario de la herida en la enfermedad del seno pilonidal.DISEÑO:Ensayo aleatorio controlado de un solo centro.AJUSTES:Hospital de enseñanza primaria en los Países Bajos.PACIENTES:Pacientes con enfermedad primaria del seno pilonidal presentados entre 2013 y 2017.INTERVENCIONES:Los pacientes fueron asignados de manera aleatoria a la escisión de la fosa del quiste y posterior administración de fenol de los tractos sinusales o a la escisión con cierre primario de la herida fuera de la línea media.PRINCIPALES MEDIDAS DE RESULTADO:Recurrencia, calidad de vida (Short-Form 36) y satisfacción del paciente.RESULTADOS:Un total de 100 pacientes con enfermedad primaria del seno pilonidal fueron aleatorizados; 50 pacientes fueron sometidos al tratamiento con fenol y 50 a la escisión radical. Eventualmente, 74 pacientes (77,1%) estuvieron disponibles para seguimiento a largo plazo; 36 pacientes después del uso del fenol y 38 después de la escisión. El tiempo medio (± desviación estándar) de seguimiento fue de 48,4 (± 12,8) y 47,8 (± 13,5) meses, respectivamente. No hubo diferencia significativa entre ambos grupos con respecto a la calidad de vida. En el grupo tratado con fenal, dos pacientes (5,6%) desarrollaron recurrencia y un paciente (2,6%) en el grupo de escisión ( p = 0,604). El impacto de todo el tratamiento fue significativamente menor después del uso del fenol (p = 0,010).LIMITACIONES:La tasa de respuesta fue de casi el 80% en esta población de pacientes jóvenes, los pacientes y los evaluadores no estaban cegados por el tipo de cirugía, los resultados son solo aplicables a la enfermedad primaria del seno pilonidal.CONCLUSIONES:Debido a los resultados favorables a corto plazo descritos y a la tasa de recurrencia a largo plazo y la calidad de vida comparables actualmente informadas entre la administración de fenol y la escisión con cierre primario de la herida para la enfermedad primaria del seno pilonidal, la administración de fenol del tracto sinusal debe considerarse como opción de tratamiento primario en pacientes con enfermedad del seno pilonidal. Consulte Video Resumen en http://links.lww.com/DCR/C27 . (Traducción-Dr. Osvaldo Gauto )Registro de prueba holandés-ID:NTR4043.

Colonoscopic-Assisted Laparoscopic Wedge Resection for Colonic Lesions: A Prospective Multicenter Cohort Study (LIMERIC-Study).

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR. SUMMARY BACKGROUND DATA: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity. METHODS: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated. RESULTS: Of the 118 patients included (56% male, mean age 66 years, standard deviation ± 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up. CONCLUSIONS: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.

Single-cell derived tumor organoids display diversity in HLA class I peptide presentation.

Tumor heterogeneity is a major cause of therapeutic resistance. Immunotherapy may exploit alternative vulnerabilities of drug-resistant cells, where tumor-specific human leukocyte antigen (HLA) peptide ligands are promising leads to invoke targeted anti-tumor responses. Here, we investigate the variability in HLA class I peptide presentation between different clonal cells of the same colorectal cancer patient, using an organoid system. While clone-specific differences in HLA peptide presentation were observed, broad inter-clone variability was even more prevalent (15-25%). By coupling organoid proteomics and HLA peptide ligandomics, we also found that tumor-specific ligands from DNA damage control and tumor suppressor source proteins were prominently presented by tumor cells, coinciding likely with the silencing of such cytoprotective functions. Collectively, these data illustrate the heterogeneous HLA peptide presentation landscape even within one individual, and hint that a multi-peptide vaccination approach against highly conserved tumor suppressors may be a viable option in patients with low tumor-mutational burden.

Phenolisation of the Sinus Tract in Recurrent Sacrococcygeal Pilonidal Sinus Disease: A Prospective Cohort Study.

Purpose Phenolisation is a minimally invasive treatment option in patients with primary pilonidal disease. However, most studies focus on patients with primary pilonidal sinus disease, while data of patients with recurrent pilonidal disease are very scarce. The purpose of this study was to evaluate phenolisation of the sinus tract in patients with recurrent pilonidal sinus disease after previous surgery for SPSD. Methods This single-center prospective cohort study included 60 patients with recurrent pilonidal disease. Loss of days of normal daily activities, surgical site infection, wound epithelization, quality of life, and complaints related to pilonidal disease were postoperatively assessed. Results A total of 57 patients (95%) were treated with phenolisation and the median loss of days of normal daily activities was 5.0 (1.0 - 12.0) days. Fifty-one patients (89.5%) resumed normal daily activities after two weeks. Surgical site infection occurred in five patients (8.8%). Compared to preoperative scores, quality of life was significantly higher 12 weeks postoperatively (p=0.014) and pain and itch scores were lower after six and 12 weeks (p ≤ 0.005). Wounds were completely healed in 45 of 51 patients (89.8%) who were available after 12 weeks of follow-up. Conclusion Phenolisation for recurrent pilonidal disease is safe with a median complete return to daily activities within five days and complete wound healing after three months in 90%. Therefore, phenolisation should be considered as a treatment option in patients with recurrent pilonidal sinus disease.

Sexual Function in Patients Suffering from Sacrococcygeal Pilonidal Sinus Disease.

Introduction Sexual function is one of the aspects upon which quality of life (QoL) is based. Although previous studies have evaluated the influence of sacrococcygeal pilonidal sinus disease (SPSD) on QoL, no data are available on the influence of SPSD on sexual function in a highly active sexual population based on the age range. The aim of this prospective study was to evaluate whether SPSD has a negative impact on sexual function and whether this is influenced by the surgical treatment of SPSD. Methods  Sexual function was pre- and postoperatively assessed by the Sexual Self-Consciousness Scale (SSCS; score range 0-48), subdivided into the sexual embarrassment (SE; score range 0-24) and sexual self-focus subscale (SFF; score range 0-24). The higher the score, the higher is the sexual dysfunction. Patients were also asked whether SPSD influenced their sexual functioning. Results  A total of 88 male patients who underwent surgical treatment for SPSD were included in the study. The mean (±SD) preoperative SSCS score was 14.5±9.1 and 13.9±8.4 two weeks postoperatively (p=0.394). Six and twelve weeks after surgery, there was a significant reduction to 12.2±9.0 (p=0.002) and 12.3±8.8 (p=0.013), respectively. SE decreased from 5.5±5.1 preoperatively to 5.1±4.6 (p=0.258), 4.2±4.7 (p=0.004) and 4.0±4.6 (p=0.013) two, six, and twelve weeks after surgery. For SFF, there was a decrease from 9.0±5.0 to 8.9±4.9 (p=0.717), 7.8±5.2 (p=0.004) and 8.2±5.3 (p=0.168), respectively. Preoperatively, 70% of the patients totally or partially disagreed that SPSD influenced their sexual functioning, and this increased to 80% of the patients 12 weeks after surgery. Conclusion  This prospective study showed a significant decrease in sexual dysfunction, both six and twelve weeks after surgery, compared to preoperatively in patients suffering from SPSD.

[Chronic pilonidal sinus disease: overview of treatment options]. / Chronische sinus pilonidalis.

Chronic pilonidal sinus disease: overview of treatment options Pilonidal sinus disease is a common disease in predominantly young men; this condition can have a significant socio-economic impact. Although excision with primary or secondary wound healing is often applied, there is no consensus on the treatment of first choice for pilonidal sinus disease. Minimally invasive techniques, such as phenolisation, laser, and endoscopic treatments are increasingly applied, since these are associated with less pain, faster wound healing and facilitating a more rapid return to work for patients. Skin advancement flap techniques, considering they cause morbidity and large wounds, should only be considered in case of recurrent pilonidal sinus disease. Laser hair removal at the natal cleft after surgical treatment appears to reduce the risk of recurrence.

Intra-tumour diversification in colorectal cancer at the single-cell level.

Every cancer originates from a single cell. During expansion of the neoplastic cell population, individual cells acquire genetic and phenotypic differences from each other. Here, to investigate the nature and extent of intra-tumour diversification, we characterized organoids derived from multiple single cells from three colorectal cancers as well as from adjacent normal intestinal crypts. Colorectal cancer cells showed extensive mutational diversification and carried several times more somatic mutations than normal colorectal cells. Most mutations were acquired during the final dominant clonal expansion of the cancer and resulted from mutational processes that are absent from normal colorectal cells. Intra-tumour diversification of DNA methylation and transcriptome states also occurred; these alterations were cell-autonomous, stable, and followed the phylogenetic tree of each cancer. There were marked differences in responses to anticancer drugs between even closely related cells of the same tumour. The results indicate that colorectal cancer cells experience substantial increases in somatic mutation rate compared to normal colorectal cells, and that genetic diversification of each cancer is accompanied by pervasive, stable and inherited differences in the biological states of individual cancer cells.

Long-term Results of a Randomized Double-blinded Prospective Trial of a Lightweight (Ultrapro) Versus a Heavyweight Mesh (Prolene) in Laparoscopic Total Extraperitoneal Inguinal Hernia Repair (TULP-trial).

OBJECTIVE: The aim of the randomized clinical trial was to compare the 2 years of clinical outcomes of a lightweight (Ultrapro) vs a heavyweight (Prolene) mesh for laparoscopic total extraperitoneal (TEP) inguinal hernia repair. BACKGROUND: Lightweight meshes reduce postoperative pain and stiffness in open anterior inguinal hernia repair. The discussion about a similar benefit for laparoscopic repair is ongoing, but concerns exist about higher recurrence rates. METHODS: Between March 2010 and October 2012, male patients who presented with a primary, reducible unilateral inguinal hernia who underwent day-case TEP repair were eligible. Outcome parameters included chronic pain, recurrence, foreign body feeling, and quality of life scores. RESULTS: During the study period, 950 patients were included. One year postoperatively the presence of relevant pain (Numeric Rating Score 4-10) was significantly higher in the lightweight mesh group (2.9%) compared with the heavyweight mesh group (0.7%) (P = 0.01), and after 2 years this difference remained significant (P = 0.03). There were 4 (0.8%) recurrent hernias in the heavyweight mesh group and 13 (2.7%) in the lightweight group (P = 0.03). No differences in foreign body feeling or quality of life scores were detected. CONCLUSIONS: In TEP hernia surgery, there was no benefit of lightweight over heavyweight meshes observed 2 years postoperatively.